LINC01106 drives colorectal cancer growth and stemness through a positive feedback loop to regulate the Gli family factors

Abstract

Long non-coding RNAs (lncRNAs) are essential contributors to the progression of various human cancers. Long intergenic non-protein coding RNA 1106 is a member of lncRNAs family. Until now, the specific role of LINC01106 in CRC remains undefined. The aim the current study was to unveil the functions of LINC01106 and explore its potential molecular mechanism in CRC. Based on the data of online database GEPIA, we determined that LINC01106 was expressed at a high level in colon adenocarcinoma (COAD) tissues compared to normal colon tissues. More importantly, high level of LINC01106 had negative correlation with the overall survival of COAD patients. Additionally, we also determined the low level of LINC01106 in normal colon tissues based on UCSC database. Through qRT-PCR, we identified that LINC01106 was highly expressed in CRC tissues compared to adjacent normal ones. Similarly, we detected the expression of LINC01106 and confirmed that LINC01106 was expressed higher in CRC cells than that in normal cells. Subsequently, LINC01106 was mainly distributed in the cytoplasm. LINC01106 induced the proliferation, migration, and stem-like phenotype of CRC cells. Mechanistically, cytoplasmic LINC01106 positively modulated Gli4 in CRC cells by serving as a miR-449b-5p sponge. Furthermore, nuclear LINC01106 could activate the transcription of Gli1 and Gli2 through recruiting FUS to Gli1 and Gli2 promoters. Mechanism of investigation unveiled that Gli2 was a transcription activator of LINC01106. In conclusion, Gli2-induced upregulation of LINC01106 aggravates CRC progression through upregulating Gli2, Gli2, and Gli4.

Long noncoding RNAs: functions and mechanisms in colon cancer

“…LINC01567 (also known as LOCCS) is highly expressed in colon CSCs that express CD133+/CD166+/CD44+, and its inhibition suppresses the proliferation, migration, invasion and tumor xenografts of colon CSCs via sponging miR-93 [ 54 ]. Recently, linc01106 confers colon cancer proliferation, migration, and stemness via regulating the Gli family factors partly by sponging miR-449b-5p [ 52 ].…”

Noncoding RNAs related to the hedgehog pathway in cancer: clinical implications and future perspectives

“…LINC01106 has been reported to facilitate proliferation and migration of colorectal cancer cells. Further investigation reveals that LINC01106 located in the nuclear could recruit FUS protein to Gli1 and Gli2 promoters, hence activating Gli1 and Gli2 transcription and promoting colorectal cancer formation [ 151 ]. Nevertheless, lncRNA HHIP-AS1 [ 152 ] acts as a tumor suppressor in HCC progression, which is attributed to its positive regulation of Hhip mRNA stability in a HuR-dependent manner.…”

Regulatory RNAs, microRNA, long-non coding RNA and circular RNA roles in colorectal cancer stem cells

“…These lncRNAs also relate to CRC prognosis. Guo et al [ 96 ] found that lncRNA1106 is highly expressed in colon adenocarcinoma and induces the proliferation, migration, and stem cell properties of CRC cells. Cytoplasmic lncRNA1106 can be used as miR-449b-5p sponge.…”